Stem cell therapy can broadly be divided into approaches aimed at de novo regeneration of injured organs, or into the use of the stem cells to accelerate endogenous healing processes. It appears that adult stem cells are stored in reservoirs ready to meet the body's need subsequent to injury. For example, in conditions as diverse as renal injury [1], myocardial infarct [2], stroke [3], irradiation [4], and acoustic damage [5], injured tissue has been reported to cause upregulation of the chemokine stromal derived factor (SDF)-1, which causes mobilization and attraction of bone marrow derived stem/progenitor cells.
Augmentation or de novo initiation of the mobilization process has been performed therapeutically using cytokines such as G-CSF [6], GM-CSF [7], and Parathyroid Hormone [8]. Recently small molecule antagonists of CXCR4 have entered clinical use [9]. Therapeutic benefits of mobilization have been seen in models of: a) radiation induced salivary gland damage [10, 11]; b) cardiac infarct [12]; c) stroke [13]. Clinically, mobilization therapy has been attempted in conditions such as ALS [14], heart failure [15, 16], and liver failure [17].
Unfortunately, agents used in the mobilization of stem cells/EPC such as G-CSF, GM-CSF, and Parathyroid Hormone are expensive and can not be continually administered for long periods of time. Thus there is a need for agents which induce augmentation of circulating stem cell/EPC levels that can be administered chronically, without adverse effects, and is relatively inexpensive. Jensen et al reported an extract from the edible cyanobacterium Aphanizomenon flos-aquae (AFA) enriched for a novel ligand for human CD62L (L-selectin), which is currently sold commercially under the name StemEnhance [18]. Although this compound is relatively innocuous from a toxicity perspective, mobilization appears to be mediated in a non-specific manner. In healthy volunteers a transient, 18% increase in numbers of circulating CD34+ stem cells was noted that maximized 1 hour after consumption. Given this relatively insignificant increase and transient nature of mobilization, as well as the fact that mechanistically mobilization is associated with decrease in CXCR4, which would block homing of stem cells to target tissue, novel methods of mobilization stem/progenitor cells are needed that are useful for long-term administration.